1. The Field of the Invention
The present invention relates to the treatment of disordered tissue with anti-infective compositions, especially antiviral, antifungal and antimicrobial compositions. More particularly, the treatment compositions include at least one of substances such as quaternary amine medicament compounds and organic compounds that have at least one carbon-halogen bond. The present invention provides a novel combination of treatment compositions and modes of applying them to treat tissue disorders, particularly epithelial tissue disorders caused by viruses, bacteria, or fungi.
2. The Relevant Technology
Tissue disorders, particularly those which impact epithelial tissue caused by all types of Herpes, such as Herpes Simplex types I and II and Herpes Zoster (shingles), candida albicans, chicken pox, acne, psoriasis, eczema, seborrhea, dermatitis, and pink eye are common but often difficult to treat. Such disorders are more likely to develop in people living with compromised sanitary conditions, the elderly, and the chronically ill. Others susceptible to such disorders include workers in health care, agricultural workers, chemical industry workers, individuals working with industrial cleaners, and painters, where chronic exposure to chemicals, pathogens, and unsanitary conditions tend to weaken and irritate epithelial tissue.
Herpes simplex virus (HSV-I and HSV-II) and Herpes Varicell—Zoster (chicken pox, shingles), commonly referred to as “herpes virus” or “herpes,” is an infectious disease which has reached crisis proportions nationally with estimated numbers of infected people at 70%-80% of U.S. population as reported by the American Social Health Association (ASHA) and growing annually by 500,000 people or more.
Herpes enters the human body through minuscule breaks in the epidermal tissue usually by contact with an infected host and is marked by eruption of one or more vesicles, usually in groups, following an incubation period of approximately two to ten days. Typically the course of the infectious outbreak initiates with the prodromal stage, advancing to vesicular eruption, followed by ulceration, coalescing, resolution, and the latency period. The outbreak can last for several weeks and on average lasts one to three weeks. In some immune compromised individuals, the outbreak can last for months. The vesicles can appear anywhere on epithelial tissues including the skin or mucosa, typically appearing on the lips as cold sores, glands, oral mucosa, conjunctiva and cornea, and genitalia, anal mucosa and peri-anal tissue as herpes genitalis.
Herpes symptoms include inguinal swelling, pain, fever, malaise, headaches, muscle aches, and swollen glands. Some individuals with oral herpes that impacts the trigeminal nerve have excruciating facial pain, difficulty swallowing, eating and facial swelling. Individuals with the herpes that impacts the sacral nerve have pain in the genital area, upper leg pain, swelling, and on occasion great difficulty walking.
Herpes simplex virus (HSV) infection is recurring, residing in the nerve ganglia, then recurring due to some, as yet unknown, stimulus. Recurrent herpetic infections can be precipitated by almost anything, including exposure to sunlight, nutritional deficiencies, stress, menstruation, immunosuppression, certain foods, drugs, febrile illness, etc.
Herpes infections pose very serious health threats, often causing blindness, increased cancer risk of the cervix, aseptic meningitis and encephalitis, neonatal deaths, viremia, the spread of the human immunodeficiency virus (HIV), etc. The devastating effects of this disease go well beyond the medical scope of human suffering; HSV is responsible for serious psychological and emotional distress as well as substantial economic loss.
Various treatments for herpes have been proposed and have included topical application of such agents as povidone-iodine, idoxuridine, trifluorothyidine, or acyclovir and its analogs. Such treatments have met with varying degrees of success. Most prior treatments have proven disappointing. Acyclovir and similar analogs, acyclic nucleosides, are taken orally for systemic treatment of HSV or they are applied topically. Acyclovir is somewhat effective in inhibiting the activity of several herpes viruses. However, acyclovir is only successful in interrupting the replication of the virus and is used to treat infectious outbreak systemically. Denavir is the topical version of an acyclovir analog. Nothing to date has proven really effective as a topical treatment. Strains resistant to acyclovir and acyclovir analogs have been reported. Individuals with Auto Immune Deficiency Syndrome (AIDS) are seriously immune-compromised and can suffer especially debilitating outbreaks of HSV. Additionally, AIDS individuals may carry acyclovir resistant strains of HSV, which can make acyclovir ineffective for these individuals. It would therefore be an improvement in the art to develop a safe and successful medical treatment to overcome the very serious problems caused by the herpes virus.
Biologically active antiviral and microbial compositions have been met with marginal success when administered topically for tissue disorders. Such compositions have been applied as gels, creams, lotions, oils, ointments, pastes, tinctures, emulsions, and colloidal suspensions. Most of the compositions are oil-based to ensure that the composition has sufficient viscosity and/or tackiness to remain on the surface of the skin. In fact, such compositions are generally absorbed into clothing more than into the skin due to a relatively slow epidermal penetration rate. Even when sufficient time is allowed for the compositions to penetrate, they are often not sufficiently effective in treating the disordered tissue.
Many efforts have been undertaken to remedy the inadequate results of topically administered compositions having antiviral and antimicrobial qualities. The therapeutic effects of such compositions depend upon the specific active agent and the method of application. Many compositions of the prior art contain ingredients that may provide symptomatic relief of pain and itching, but are not claimed to be effective against Herpes infection except the drugs based on acyclovir technology, which are purported to have some topical efficacy. Additionally, most compositions intended to treat such disorders do not effectively treat the discomfort and the disease symptoms, let alone cure the disorder or put it into a significant remission.
Examples of conventional application methods and compositions are provided in WO 98/42188 and in WO 98/11778 by Squires, both of which are hereby incorporated by reference. In WO 98/42188 at page 9, lines 12-18 and in WO 98/11778 at page 5, lines 22-30, it is stated that the composition is applied by “spraying, dabbing, dusting, swabbing, sponging, brushing, pouring, dispensing, covering or heavily coating.” The stated objective of these techniques for applying the composition is to insure that the composition remains on the infected area. Like other conventional treatment compositions, the composition has a viscosity and/or tackiness which enables it to remain on the surface of the infected area. A portion of such compositions may eventually penetrate beyond the surface of the disordered tissue such as the outer surface of skin or a lip; however, the viscosity of the composition, combined with the application technique, prevents such compositions from achieving effective penetration.
Another example of conventional application methods and compositions is provided in U.S. Pat. No. 5,753,270 to Beauchamp et al., which is also incorporated by reference. U.S. Pat. No. 5,732,270 discloses a composition which includes: (a) an antiseptic and/or anesthetic compound which is (i) a terpene, such as menthol or eucalyptol or (ii) a phenolic compound, such as thymol; (b) a quaternary ammonium antiseptic compound, such as benzethonium chloride; and (c) an antiseptic compound containing iodine, salts thereof and/or complexes thereof dissolved in an organic skin penetrating solvent, such as a mixture of water and acetone. The methodology is described in the examples provided at columns 5-7 as involving the liberal application of the composition to the afflicted area in a sequence such as 3 to 4 applications over a one minute period which is then repeated every 3 minutes over a 10 minute period. The entire procedure is then repeated after approximately ½ to 1 hour for 2 to 3 hours or until activity is stopped in healing is evident. The use of a cotton swab is mentioned at column 6, lines 10-11 for applying the composition.
Although it is mentioned in U.S. Pat. No. 5,753,270 at column 3, lines 44-49 that the formulations may be prepared as a gel, cream, a lotion, an ointment, or a paste, the preferred embodiment appears to be a solution having an aqueous solvent system. It is noted at column 3, lines 6-9 that although use of water and acetone as a solvent is preferred, such a solvent is not considered essential to the overall synergistic action of the formulation. In any event, the formulation appears not to rely on either its viscosity or tackiness to ensure that the formation is maintained on the surface of the afflicted area as do most conventional compositions. Rather the methodology involves the very frequent reapplication of the formulation to the afflicted area. Some of the formulation may be absorbed into the skin; however, a significant portion is likely rapidly evaporated due to the high content of water and acetone.
The active agents disclosed in U.S. Pat. No. 5,753,270 that are discussed above include at least one compound which is an antiseptic and/or an anesthetic. The primary examples of such compounds—menthol, eucalyptol, and thymol—are either obtained from natural sources, such as naturally occurring oils, or are derived from such oils. Eucalyptol is described as being an essential oil and a terpene ether. Thymol is derived from thyme oil or other oils. Menthol is obtained from peppermint oil or other oils. Other suitable compounds are also recited in the claims as including eugenol, camphor, hexetidine, or anethol. While the basis for inclusion of hexetidine in this grouping is not clear, the other chemicals are also obtained from natural sources or are derived therefrom. Eugenol is obtained by extraction of clove oil and then chemical modification. Camphor is a ketone which occurs naturally in the wood of the camphor tree. Anethol is derived from anise or fennel oils. While these compounds are useful, particularly as antifungal agents, it is doubtful that they assist in penetrating the afflicted tissue and may in fact retard penetration or enhance the skin's natural resistance to penetration. The FDA does not consider these compounds as useful in the treatment of herpes, rather they are used for their softening effects.
In conclusion, significant medical research in this field of endeavor has been focused on developing compositions used for treating affected tissues and yet compositions which provide rapid relief to these ailments are still needed. It would therefore be an improvement in the art to provide compositions, systems and methods for treating tissue disorders (such as epithelial tissue disorders0 that overcome the problems of the prior art.
Such compositions, methods and systems of application are taught and claimed herein.